RNA oligomers at atomic resolution containing 1-methylpseudouridine, an essential building block of mRNA vaccines.

All widely used mRNA vaccines against COVID-19 contain in their sequence 1-methylpseudouridine (m1Ψ) instead of uridine. In this publication, we report two high resolution crystal structures (at up to 1.01 and 1.

Contrasting reactivity of thioglucoside and selenoglucoside donors towards promoters: implications for glycosylation stereocontrol.

The stereochemical outcome of glycosylation reactions with model thioglycosides and selenoglycosides proved to be dependent on the source of promoter iodonium ion, with iodine giving different results to N-iodosuccinimide (NIS) alone or N-iodosuccinimide/trimethylsilyltrifluoromethanesulfonate (NIS/TMSOTf). In contrast to armed thioglycosides, which anomerise, and disarmed thioglycosides, which do not react, both armed and disarmed selenoglycosides give rise to the corresponding glycosyl iodides when reacted with iodine. Further, whilst the single electron transfer agent DDQ alone is an ineffective promoter, in combination with iodine it produces better acetonitrile-assisted beta-stereoselectivity with both thioglycosides and selenoglycosides than does tris(4-bromophenyl)aminium hexachloroantimonate (BAHA).

From solution phase to "on-column" chemistry: trichloroacetimidate-based glycosylation promoted by perchloric acid-silica.

[reaction: see text] Activation of ester-protected glycosyl trichloroacetimidate donors by perchloric acid immobilized on silica afforded 1,2-trans disaccharides in 60-90% yields. Applying this approach to one-pot sequential glycosylation resulted in efficient syntheses of the N-linked glycan trimannoside and Le(X) and Le(A) trisaccharides in very good yield (76%, 62%, and 59% yields, respectively). Solution phase reactions were also translated to a solid phase format; priming the top of a standard silica chromatography column with perchloric acid immobilized on silica facilitated "on-column" glycosylation with subsequent "in situ" purification of products.

A practical synthesis of gramicidin s and sugar amino Acid containing analogues.

A practical gram-scale and high-yielding synthesis of the antimicrobial peptide gramicidin S is presented. An Fmoc-based solid-phase peptide synthesis protocol is employed for the generation of the linear decapeptide precursor, which is cyclized in solution to afford the target compound. The versatility of our method is demonstrated by the construction of eight gramicidin S analogues (15a-h) having nonproteinogenic sugar amino acid residues (4-7) incorporated in the turn regions.

Conformational analysis of furanoid epsilon-sugar amino acid containing cyclic peptides by NMR spectroscopy, molecular dynamics simulation, and X-ray crystallography: evidence for a novel turn structure.

Sugar amino acids (SAAs) are useful building blocks for the design of peptidomimetics and peptide scaffolds. The three-dimensional structures of cyclic hybrid molecules containing the furanoid epsilon-SAA III and several amino acids were elucidated to study the preferred conformation of such an epsilon-SAA and its conformational influence on the backbone of cyclic peptides. NMR-based molecular dynamics simulations and empirical calculations of the cyclic tetramer 1, consisting of two copies of the SAA residue and two amino acids, revealed that it is conformationally restrained.

Solid-phase synthesis of cyclic RGD-furanoid sugar amino acid peptides as integrin inhibitors.

The solid-phase synthesis of cyclic RGD peptides containing either one or two furanoid sugar amino acids (SAAs) is reported. Using a cyclization-cleavage approach five peptides were successfully assembled and consecutively tested on their ability to bind to the integrin receptors alpha(v)beta(3) and alpha(IIb)beta(3). The cyclic tetrapeptide c[RGD-SAA] (1) showed the most promising activity in an inhibition assay with an IC(50) of 1.